Μ-oxo Dimer Research Articles

Interaction of quinoline antimalarial drugs with ferriprotoporphyrin IX, a solid state spectroscopy study

To investigate the nature of binding of quinoline antimalarial drugs to heme and to extract experimental evidence for this binding, the interaction of ferriprotoporphyrin IX (FP) with chloroquine and quinacrine (both of which have a similar side chain) and quinoline methanol antimalarials quinine and mefloquine has been studied using IR and NIR-Raman spectroscopy in the solid state. Attenuated total reflectance infrared spectroscopic data clearly show that heme in chloroquine–FP complex is not μ-oxo dimeric indicating that the hypothesis that chloroquine binds to FP μ-oxo dimer with a stoichiometry of 1 chloroquine:2 μ-oxo dimers is not valid in the solid state. Moreover, the first vibrational spectroscopy evidence is presented for the formation of hydrogen bonding between a propionate group of heme and the tertiary amino nitrogen of chloroquine and quinacrine. Raman spectroscopy data does not provide any evidence to support the formation of a similar salt bridge in the complexes of FP with quinine and mefloquine; however, it suggests that the interaction of these drugs with FP happens through coordination of the Fe(III) center of the porphyrin to the 9-hydroxy group of the drug.

Gold Nanoparticles Carrying Diatomic Molecules (O2 and CO) in Aqueous Solution

Gold nanoparticles (AuNPs) prepared by citrate reduction of aurochloric acid (HAuCl(4)) were functionalized by tris(4-sulfonatophenyl)porphinatoiron(III) (Fe(III)P2) and poly(ethylene glycol) with thiolated arms (PEG-SH). Fe(III)P2 on the AuNP surface existed as its μ-oxo dimer, which was reduced by Na(2)S(2)O(4) to yield monomeric Fe(II)P2. Fe(II)P2-bearing AuNPs were further functionalized through inclusion of two sulfonatophenyl groups of Fe(II)P2 by a per-O-methylated β-cyclodextrin dimer with a pyridine linker (Py3CD) to obtain AuNPs capable of carrying diatomic molecules in the body. The resulting AuNPs (hemoCD-AuNPs) bound O(2) as well as CO in an aqueous solution. Although a noncolloidal 1:1 complex of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphinatoiron(II) and Py3CD injected into the femoral vein of a rat was rapidly excreted in the urine, no excretion was observed with ferric hemoCD-AuNPs, which were gradually accumulated in the spleen and liver of a rat. These results suggest that hemoCD-AuNPs can be used as a carrier of diatomic molecules such as O(2) and CO in vivo.

Iron(III) complexes of N2O and N3O donor ligands as functional models for catechol dioxygenase enzymes: ether oxygen coordination tunes the regioselectivity and reactivity

A series of mononuclear iron(III) complexes of the type [Fe(L)Cl(3)], where L is a systematically modified N(2)O or N(3)O ligand with a methoxyethyl/tetrahydrofuryl ether oxygen donor atom, have been isolated and studied as models for catechol dioxygenases. The X-ray crystal structures of [Fe(L2)Cl(3)] 2, [Fe(L6)Cl(3)] 6, [Fe(L5)(TCC)Cl] 5a, where H(2)TCC = tetrachlorocatechol, [Fe(L6)(TCC)Br] 6a, and the μ-oxo dimer [{Fe(L6)Cl}(2)O](ClO(4))(2) 6b have been successfully determined. In [Fe(L2)Cl(3)] 2 the N(2)O ligand is facially coordinated to iron(III) through the pyridine and secondary amine nitrogen atoms and the tetrahydrofuryl oxygen atom. In [Fe(L6)Cl(3)] 6, [Fe(L5)(TCC)Cl] 5a and [Fe(L6)(TCC)Br] 6a the N(3)O donor ligands L5 and L6 act as a tridentate N3 donor ligand coordinated through two pyridine and one secondary amine nitrogen atoms, whereas the ether oxygen is not coordinated. The spectral and electrochemical properties of the adducts [Fe(L)(DBC)Cl] of 1-8, where H(2)DBC = 3,5-di-tert-butylcatechol, in DMF and their solvated adduct species [Fe(L)(DBC)(Sol)](+), where Sol = DMF/H(2)O, generated in situ in dichloromethane, respectively, have been investigated. The product analysis demonstrates that the adducts [Fe(L)(DBC)Cl] effect cleavage of catechol in the presence of O(2) in DMF to give mainly the intradiol (I) product with a small amount of the extradiol (E) product (E/I, 0.2:1-0.7:1). Interestingly, the solvated species [Fe(L)(DBC)(Sol)](+) derived from 1-4 cleave H(2)DBC to provide mainly the extradiol cleavage products with lower amounts of intradiol products (E/I, 2.3:1-4.3:1) in dichloromethane. In contrast, the solvated species [Fe(L)(DBC)(Sol)](+) derived from 5-8 cleave H(2)DBC to provide both extradiol and intradiol products (E/I, 0.6:1-2.3:1) due to the involvement of the ether oxygen donor of the methoxyethyl/tetrahydrofuryl arm in the coordination to iron(III) upon removal of a chloride ion.

Selective oxygenation of α-olefins by means of metalloporphyrin catalysts mimicking cytochrome P-450

A significant problem associated with synthetic metalloporphyrin catalysts used to mimic oxygenation function of cytochrome P-450 is their deactivation due to the formation of inactive μ-oxo dimer. We prepared a series of porphyrin-based catalysts mimicking cytochrome P-450 potentially resistant to deactivation by varying the central metal ion, porphyrin ring substitution, and catalyst support. The influence of the nature of a solid support, the type of central cation and the chemical modification of the porphyrin ring on the catalytic efficiency was studied. The oxygenation ability of the synthesized catalysts was tested using 1-hexene as a substrate and tert-butyl hydroperoxide as an oxidant under various reaction conditions. Identification of the oxygenation products was performed with gas chromatography-mass spectrometry (GC-MS). Quantification of the products formed was based on GC with flame ionization detection (FID). It was found that the application of low GC injection temperature (150 °C) was necessary to detect primary products of the oxygenation, peroxo alkenes, from which secondary oxygenation products, mainly epoxides, alcohols, aldehydes and ketones, were formed slowly. The efficiency of the individual catalysts depended on their structure and varied significantly. The most active catalysts were Fe(II)-tetraphenylporphyrin (TPP) immobilized on aminopolystyrene (aminoPS) and Mn(II)-TPP immobilized on aminoPS.

A Remarkably Bent Diiron(III)-μ-Hydroxo Bisporphyrin: Unusual Stabilization of Two Spin States of Iron in a Single Molecular Framework

A novel diiron(III) bisporphyrin bridged by a hydroxo group between two cofacial Fe centers is reported. X-ray structural characterization revealed the remarkably bent μ-hydroxobis[Fe(III) porphyrin] with the smallest known Fe-O(H)-Fe angle [142.5(2)°] reported to date in an iron porphyrin. The close approach of the two rings in the molecule results in an unequal core deformation, and as a result, the geometrical parameters (such as the Fe-N(p), Fe-O and Fe···Ct(p) distances) are all different for the two Fe(III) centers, leading for the first time to a natural way of stabilizing two different spins of iron in a single molecular framework with complete retention of their own spectroscopic identities in both the solid state and solution. The strong antiferromagnetic coupling between the two Fe(III) centers in the μ-oxo dimer (-J = 126.6 cm(-1)) is attenuated to only 4.5 cm(-1) simply by protonation to give the μ-hydroxo complex.

ChemInform Abstract: Oxidation of Ethylbenzene (Derivatives) Catalyzed by a Functionalized Ionic Liquid Combined with Cationic (Tetrakis(N‐methyl‐4‐pyridinium)porphyrinato)manganese(III) and Anionic Phosphotungstate.

A functionalized ionic liquid (IL) combined with cationic (tetrakis(N-methyl-4-pyridinium)porphyrinato)manganese(III) and anionic phosphotungstate was prepared and applied as the catalyst for ethylbenzene (derivative) oxidations without involvement of the auxiliary axial ligands. A synergetic catalytic effect between the cations and the counteranions in this functionalized IL was observed in terms of activity and stability. Although anionic phosphotungstate ([PW12O40]3−) showed negligible contribution to the activation of ethylbenzene, it stabilized the manganese porphyrin against oxidative degradation. The in situ UV-Vis analysis of the oxidation of the functionalized IL by PhIO indicated that with the incorporation of [PW12O40]3− as the counteranion the formation of the μ-oxo MnIV porphyrin dimer was completely suppressed, resulting in improved catalytic performance for the corresponding manganese porphyrin.

Rhenium Complexes with 2-(Diphenylphosphinomethyl)aniline: Formation of a Cyclic, Trinuclear Oxorhenium(V) Core

Reactions of 2-(diphenylphosphinomethyl)aniline, H(2)L(2), with (NBu(4))[ReOCl(4)] yield different oxo rhenium(V) complexes depending on the conditions applied. This comprises monomeric compounds such as [ReOCl(3)(H(2)L(2))] (1), [ReOCl(2)(OMe)(H(2)L(2))] (2), or [ReO(2)(H(2)L(2))(2)]Cl (5) as well as the dimeric μ-oxo complex [{ReOCl(2)(H(2)L(2))}(2)]O] (3) and the oxo-bridged trimer [{ReOCl(H(2)L(2))}O](3) (4). The latter compound represents the first example of a hitherto unknown trinuclear, cyclic oxo(V) core. [{ReOCl(H(2)L(2))}O](3) contains a tensed 6-membered metallacycle, which readily undergoes rearrangements and reactions with additional ligands. Compounds of the compositions 5 and [ReO(2)(H(2)L(2))(H(2)L(1))]Cl (6) were isolated either from the decomposition of 4 in CH(2)Cl(2)/n-pentane or from reactions with 2-(diphenylphosphino)aniline, H(2)L(1).

Oxidation of ethylbenzene (derivatives) catalyzed by a functionalized ionic liquid combined with cationic (tetrakis(N-methyl-4-pyridinium)porphyrinato)manganese(III) and anionic phosphotungstate

A functionalized ionic liquid (IL) combined with cationic (tetrakis(N-methyl-4-pyridinium)porphyrinato)manganese(III) and anionic phosphotungstate was prepared and applied as the catalyst for ethylbenzene (derivative) oxidations without involvement of the auxiliary axial ligands. A synergetic catalytic effect between the cations and the counteranions in this functionalized IL was observed in terms of activity and stability. Although anionic phosphotungstate ([PW12O40]3−) showed negligible contribution to the activation of ethylbenzene, it stabilized the manganese porphyrin against oxidative degradation. The in situ UV-Vis analysis of the oxidation of the functionalized IL by PhIO indicated that with the incorporation of [PW12O40]3− as the counteranion the formation of the μ-oxo MnIV porphyrin dimer was completely suppressed, resulting in improved catalytic performance for the corresponding manganese porphyrin.

Synthesis and Characterization ofanti-bisFe(III) Porphyrins,syn-bisFe(III)-μ-oxo Porphyrin, andsyn-bisFe(III)-μ-oxo Porphyrin Cation Radical

BisFe(III) porphyrins bridged by a highly flexible ethane linker are reported in which the bisporphyrin platform "opens" and "closes" its binding pockets leading to facile syn-anti conformational switching with very high vertical flexibility in a single molecular framework. With axial ligand X (X: Cl, Br, I, ClO(4)), the anti-forms of the molecule are stabilized. The X-ray structure of anti bis perchloratoFe(III)porphyrin is reported, and the molecule is found to be high-spin in nature. In sharp contrast, all other Fe(III) porphyrins with ClO(4) as axial ligands are in an either intermediate or admixed spin state. The very strong Fe-OClO(3) bond and relatively weaker Fe-N(p) bonds are responsible for the high-spin nature of the molecule. Upon treatment with base, bis Fe(III)-mu-oxo porphyrin is generated in which the Fe-O-Fe unit is remarkably bent (with a 147.9(1) degrees angle) and two porphyrin rings in a molecule are so close that at least six carbon atoms from each of the porphyrin macrocycles are driven to be essentially closer than the van der Waals contact distance. Upon manipulating the acidity/basicity of the solution, the facile syn-anti conformational switching takes place that is also reversible in nature. The complex catalyzes the rapid photoinduced oxygenation of phosphites under mild condition using aerial O(2). Electrochemical data reveals that bis Fe(III)-mu-oxo porphyrin undergoes four one electron oxidations and one electron reduction. However, oxidations become easier in syn Fe(III)-mu-oxo dimer rather than the anti-form of the molecule (with axial ligand X). The presence of two porphyrin macrocycles within a short distance in the syn form makes the porphyrin core highly nonplanar and more electron rich, and that might be responsible for easier oxidations compared to [Fe(OEP)](2)O. Oxidations of the mu-oxo complex are performed using both chemical and electrochemical methods. The addition of 1.00 mol equiv of iodine-silver perchlorate generates the singly oxidized product that shows large isotropic shifts in (1)H NMR with eight diastereotopic methylene proton signals (at 295 K) spreading over 8 to 16 ppm, and two meso resonances occurs at -10.2 and -13.7 ppm in 2:1 ratio. However, the addition of less than 1 equiv of oxidizing agent gives an average (1)H NMR signal. This indicates that intra- and intermolecular electron transfer is rapid in the NMR time scale, and no porphyrin structural modification has occurred during oxidation.

Electrochemical study with cavity microelectrode containing clay-supported Mn (III)salen complex – Dioxygen activation with cytochrome P450 model

Mn IIICl–salen complex of tetradentate Schiff base ligand was incorporated into layers of clay montmorillonite by using an in situ flexible ligand method. The obtained modified clay was examined by X-ray diffraction, FT-IR and by using a cavity microelectrode (CME) to perform the electrochemical studies of the catalyst in the supported solid phase. Experiments show a well-defined and chemically reversible redox system of the manganese complex incorporated into the clay, similar to that observed in solution but with apparent diffusion coefficient around 2.3 × 10 −9 cm −2 s −1. Dioxygen activation in catalytic conditions that was found to be efficient in the modified material is studied with the CME. It demonstrates the absence of formation of μ-oxo dimers and peroxo-bridged compounds and a good penetration of the different reactants into the clay. Moreover, this analysis illustrates the interest of CME as a powerful tool for the study of similar supported catalyst implying the biomimetic activation of molecular oxygen.

Microkinetic analysis of the epoxidation of styrene catalyzed by (porphyrin)Mn encapsulated in molecular squares

Experiments and microkinetic modeling were used to investigate the kinetics of styrene epoxidation catalyzed by (porphyrin)Mn using iodosylbenzene. While the kinetics follow the general form of Michaelis–Menten rate expressions as proposed in the literature, these simplified rate forms cannot capture all the details of the kinetics simultaneously, most notably catalyst deactivation. In contrast, a microkinetic model based on elementary steps, including deactivation via μ-oxo dimer formation and irreversible degradation, is able to capture experimental data over all reaction times and for different (porphyrin)Mn. Experimentally, we show that encapsulation of (porphyrin)Mn in a supramolecular cavity known as a molecular square significantly reduces catalyst deactivation, which is in agreement with previous experimental studies. Microkinetic modeling also captured the kinetics of this system. Net rate analysis revealed that production of epoxide was primarily due to encapsulated catalysts, and the model was able to quantify the difference in the concentration of deactivated catalyst with and without encapsulation.

Aggregated Enhanced Raman Scattering in Fe(III)PPIX Solutions: The Effects of Concentration and Chloroquine on Excitonic Interactions

Resonance Raman spectra of hematin and hemin solutions are reported for 413 and 514 nm excitation wavelengths. Enhancement of A1g modes (1569 and 1370 cm(-1)) and B1g modes (1124 and 755 cm(-1)) as a function of increased concentration are observed when irradiating with 514 nm laser excitation but not 413 nm. This can be rationalized by considering an excitonic coupling mechanism. As the concentration of hematin increases there is an increased probability of supramolecular interactions between iron(III) protoporphyrin IX (Fe(III)PPIX) units occurring. The Fe(III)PPIX concentration reaches a saturation point in solution and excitonic coupling reaches a maximum causing the enhancement profile to plateau when applying 514 nm excitation. In contrast, when using 413 nm excitation there were no changes in band intensity with increased concentration showing that excitonic coupling through supramolecular interactions for aggregated solutions is wavelength dependent. Electronic absorption spectra show that as the concentration of Fe(III)PPIX increases in solution the Soret band is slightly blue shifted and the Q-band significantly broadens supporting the excitonic hypothesis. Understanding the mechanism that accounts for the Raman photophysical behavior of hemes at high concentrations provided an indirect method to monitor antimalarial drug interactions. A second aim was to investigate chloroquine binding to Fe(III)PPIX-OH/H2O monomers, pi-pi dimers and micro-oxo dimers formed in highly concentrated solutions approaching those of the digestive vacuole of the P. falciparum malaria parasite using excitonic Raman enhancement. It was hypothesized that the Raman excitonic enhancement mechanism could be impeded in heme aggregated solutions by the addition of chloroquine. This would result in a reduction in heme bands associated with the A1g modes including nu4. Resonance Raman spectra recorded using 514 nm excitation show that chloroquine (CQ) acts as a molecular spacer and binds noncovalently through dispersion interactions giving rise to pi-pi interactions, between micro-oxo dimer units of Fe(III)PPIX as evinced by the decrease in intensity of nu4 in the Raman spectrum as a function of increasing CQ mole ratio. In comparison, electronic spectra show that CQ can bind to the unligated face of Fe(III)PPIX-OH/H2O monomers, potentially reducing the formation of pi-pi dimers. This study has important implications in determining the effectiveness of potential antimalarial compounds that are thought to exert their effectiveness by binding through supramolecular interactions to the unligated faces of Fe(III)PPIX-OH/H2O monomers and micro-oxo dimers.

Production of a Putative Iron(V)−Oxocorrole Species by Photo-Disproportionation of a Bis-Corrole−Diiron(IV)−μ-Oxo Dimer: Implication for a Green Oxidation Catalyst

Photodisproportionation of a bis-corrole-diiron(IV)-mu-oxo dimer gave a corrole-iron(III) species and a corrole-iron(V)-oxo species that can be detected and studied in real time. Air oxidation of the corrole-iron(III) species regenerated the bis-corrole-diiron(IV)-mu-oxo dimer, allowing the development of a photocatalytic method for organic oxidations using molecular oxygen and visible light.

Lipopolysaccharide biosynthesis-related genes are required for colony pigmentation of Porphyromonas gingivalis

The periodontopathic bacterium Porphyromonas gingivalis forms pigmented colonies when incubated on blood agar plates as a result of accumulation of mu-oxo haem dimer on the cell surface. Gingipain-adhesin complexes are responsible for production of mu-oxo haem dimer from haemoglobin. Non-pigmented mutants (Tn6-5, Tn7-1, Tn7-3 and Tn10-4) were isolated from P. gingivalis by Tn4351 transposon mutagenesis [Hoover & Yoshimura (1994), FEMS Microbiol Lett 124, 43-48]. In this study, we found that the Tn6-5, Tn7-1 and Tn7-3 mutants carried Tn4351 DNA in a gene homologous to the ugdA gene encoding UDP-glucose 6-dehydrogenase, a gene encoding a putative group 1 family glycosyltransferase and a gene homologous to the rfa gene encoding ADP heptose-LPS heptosyltransferase, respectively. The Tn10-4 mutant carried Tn4351 DNA at the same position as that for Tn7-1. Gingipain activities associated with cells of the Tn7-3 mutant (rfa) were very weak, whereas gingipain activities were detected in the culture supernatants. Immunoblot and mass spectrometry analyses also revealed that gingipains, including their precursor forms, were present in the culture supernatants. A lipopolysaccharide (LPS) fraction of the rfa deletion mutant did not show the ladder pattern that was usually seen for the LPS of the wild-type P. gingivalis. A recombinant chimera gingipain was able to bind to an LPS fraction of the wild-type P. gingivalis in a dose-dependent manner. These results suggest that the rfa gene product is associated with biosynthesis of LPS and/or cell-surface polysaccharides that can function as an anchorage for gingipain-adhesin complexes.

Metallo-deuteroporphyrin complexes derived from heme: A homogeneous catalyst for cyclohexane oxidation

Metallo-deuteroporphyrins [M(DPDME)], where M = Co(II), Ni(II), Cu(II), or Zn(II), were synthesized and used as catalysts for cyclohexane oxidation with air in the absence of additives and solvents. These complexes provide effective catalysts for cyclohexane oxidation with air when the reaction temperature was higher than 110 °C and pressure was greater than 0.4 MPa. The research results showed that the yields of cyclohexanol and cyclohexanone, the conversion of cyclohexane and the turnover number of catalysts were influenced by the central metal, reaction temperature, pressure of air and the amount of catalyst. The catalytic activity of Co(II) (DPDME) is superior to those of Ni(II), Cu(II) and Zn(II) deuteroporphyrins. The alcohol and ketone were formed to 84.63% selectivity at a cyclohexane conversion of 18.58% under the optimum conditions. Finally, we put forward the possible mechanism of the oxidation of cyclohexane by air catalyzed by M(DPDME). In the reaction, the formation of μ-oxo dimer may be the vital process.

Quinine and Chloroquine Differentially Perturb Heme Monomer−Dimer Equilibrium

Nuclear magnetic resonance (NMR) measurements of magnetic susceptibility have been utilized to study the equilibrium between two forms (high-spin monomer vs the antiferromagnetically coupled mu-oxo dimer) of ferriprotoporphyrin(IX) as a function of pH. The pH dependence of this equilibrium is significantly altered by the addition of either chloroquine or quinine. Chloroquine promotes the mu-oxo dimer whereas quinine promotes the monomer.

The Thermodynamic Characteristics of Sublimation of Aluminum and Indium Complexes with Tetraphenylporphin according to the High-Temperature Mass Spectrometry Data

The thermodynamic characteristics of vaporization of meso-tetraphenylporphin complexes (X)MTPP (M = Al, In; X = Cl, OH; TPP is the meso-tetraphenylporphin H2TPP dianion) were studied by the Knudsen effusion method with mass spectrometric control of vapor composition. Chloride complexes sublimed as monomers over the temperature range 480–590 K. The hydroxo complex of aluminotetraphenylporphin was transferred into the gas phase in the form of the μ-oxo dimer. The temperature dependences of saturated vapor pressure were used to determine the enthalpies of sublimation of metalloporphyrins, which were found to be 203 ± 3.5 and 207 ± 6 kJ/mol for the chloride complexes of In and Al, respectively, and 206 ± 8 and 406 ± 40 kJ/mol for the monomer and μ-oxo dimer of (hydroxy)aluminum(III)porphyrin, respectively. The thermodynamic parameters of vaporization and the melting point of (OH)AlTPP were also determined (ΔvapH° = 116 ± 6 kJ/mol, ΔapS° = 72 ± 11 J/(mol K), and Tm = 579 K). Composition-thermodynamic property correlations were analyzed for metalloporphyrins.

Isolable Iron(II)–Porphycene Derivative Stabilized by Introduction of Trifluoromethyl Groups on the Ligand Framework

Abstract Two iron porphycene complexes having four trifluoromethyl groups, chloro-2,7,12,17-tetraethyl-3,6,13,16-tetrakis(trifluoromethyl)porphycenatoiron(III) [FeIIIClEtio(CF3)4Pc] and its μ-oxo dimer [{FeIIIEtio(CF3)4Pc}2(μ-O)], were characterized. The μ-oxo dimer was easily converted into the monomeric iron(II) complex via the Fe–O bond cleavage in pyridine. This is the first study to obtain a stable iron(II) species in a series of porphycene iron complexes. The iron(II) species crystallized in the monoclinic system C2⁄m, and the Fe–Npyridyl (2.007 Å) and Fe–Npyrrolyl (1.958 Å) bonds were remarkably short distances among the bispyridine-coordinated iron(II) porphyrins and porphyrinoids. To evaluate the influences of the CF3 substituents and framework structure on the autoreduction, we compared the reactivity of [{FeIIIEtio(CF3)4Pc}2(μ-O)] in pyridine with the reference iron porphycene and porphyrins. Autoreduction of [{FeIIIEtio(CF3)4Pc}2(μ-O)] smoothly proceeded at 20 °C in pyridine, whereas the reaction of the μ-oxo-bis{2,7,12,17-tetraethyl-3,6,13,16-tetramethylporphycenatoiron(III)} [{FeIIIEtio(CH3)4Pc}2(μ-O)] was converted into the monomeric iron(III) complex, and the iron(II) species was not available. In contrast, the μ-oxo-bis{1,3,5,7-tetrakis(trifluoromethyl)-2,4,6,8-tetraethylporphyrinatoiron(III)}[{FeIIIEtio(CF3)4Por}2(μ-O)] as a structural isomer of [{FeIIIEtio(CF3)4Pc}2(μ-O)] allowed the autoreduction, although the reaction was very slow and took over one month. These results indicate that the introduction of strong electron-withdrawing groups at the pyrrole β-carbons exhibits a unique reactivity of the iron complex.

Synthesis and Characterization of meso-Triarylsubporphyrins

The synthesis of several meso-triaryl-subporphyrins, based on utilizing tripyrrolylborane as a precursor in a reaction with arylaldehydes (where aryl = phenyl, 4- and 3-pyridyl, tolyl, 4-methoxyphenyl, and 4-(trifluoromethyl)phenyl) under reflux in propionic acid, is reported. All of the compounds have been successfully characterized by 1H-, 13C-, and 13C-1H 2D NMR, electronic absorption, magnetic circular dichroism (MCD), IR, and fluorescence spectroscopy, together with cyclic (CV) and differential pulse (DPV) voltammetry. The X-ray structure of tris{(trifluoromethyl)phenyl}subporphyrin was found to be slightly domed and similar to that of the recently reported hexaethylsubtriazaporphyrin (Inorg. Chem. 2006, 45, 6148). The electronic absorption spectra of all of the subporphyrins contain intense Soret bands in the 370-380 nm region and weaker Q bands in the 420-550 nm region, which are at shorter wavelengths than those observed (at ca. 400-420 nm and ca. 450-650 nm, respectively) for tetrapyrrole porphyrins. The intensity of the Q00 band decreases as the meso-aryl groups become more electron withdrawing. These characteristics can be rationalized by using Gouterman's four-orbital model as a conceptual framework. The MCD bands observed in the Q band region of the subporphyrins (subPs) spectra consistently show a -ve/+ve intensity pattern in ascending energy, while, in contrast, the sign sequence of the bands observed in the Soret band region change dramatically depending on the nature of the aryl groups: from +ve/-ve in the case of the electron withdrawing 4-pyridyl, 4-(trifluoromethyl)phenyl and 3-pyridyl groups to -ve only for phenyl and -ve/+ve for the electron donating 4-tolyl and 4-methoxyphenyl groups. S1 fluorescence emission was observed in the 490-620 nm region. The quantum yields (phiF) in benzene (phiF = 0.10-0.12) are similar to that of metal-free tetraphenylporphyrin (H2TPP) (phiF = 0.11) but are somewhat lower in the case of ethanol (phiF = 0.06-0.07) due to the higher polarity. The redox potential differences observed between the first oxidation and reduction steps are in the 2.52-2.64 V range, which is larger than that of normal porphyrins (ca. 2.25 V). Molecular orbital (MO) calculations of these compounds help to provide an enhanced understanding of the spectroscopic and electrochemical properties. A byproduct of the synthesis was characterized using X-ray crystallography and a range of spectroscopic techniques. A subporphyrin mu-oxo dimer was prepared and characterized.

Sequential action of R- and K-specific gingipains of Porphyromonas gingivalis in the generation of the heam-containing pigment from oxyhaemoglobin

The arginine- and lysine-specific gingipains of Porphyromonas gingivalis have been implicated in the degradation of haemoglobin from which the black μ-oxo haem dimer-containing pigment is generated. Here, we examined interactions of oxyhaemoglobin (oxyHb) with the Arg-(R)-specific (HRgpA) and Lys-(K)-specific (Kgp) gingipains. Incubation of oxyHb with HRgpA resulted in formation of methaemoglobin (metHb), which could be prevented by the R-gingipain specific inhibitor leupeptin. oxyHb–Kgp interactions resulted in formation of a haemoglobin haemichrome. This was inhibited by the lysine-specific protease inhibitor Z-Phe-Lys-acyloxymethylketone (Z-FKck). metHb, formed by treatment of oxyHb with either NaNO 2 or by pre-incubation with HRgpA, was rapidly degraded by Kgp compared to oxyHb. metHb degradation by Kgp was also inhibited Z-FKck. Together these data show that R-gingipain activity is crucial for converting oxyHb into the metHb form which is rendered more susceptible to Kgp degradation for the eventual release of iron(III) protoporphyrin IX and production of the μ-oxo haem dimer. This explains previous observations [J.W. Smalley, M.F. Thomas, A.J. Birss, R. Withnall, J. Silver, Biochem. J. 379 (2004) 833–840.] of the requirement for a combination of both R- and K-gingipains for pigment production from oxyhaemoglobin by P. gingivalis.